Variant rs11202607 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000314.8(PTEN):c.*2185C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 219,966 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.068 ( 419 hom., cov: 31)

Exomes 𝑓: 0.071 ( 170 hom. )

Consequence

PTEN
NM_000314.8 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.281

Variant links:

Genes affected

PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

PTEN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-87967657-C-T is Benign according to our data. Variant chr10-87967657-C-T is described in ClinVar as [Benign]. Clinvar id is 301483.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PTEN	NM_000314.8 linkuse as main transcript	c.*2185C>T	3_prime_UTR_variant	9/9	ENST00000371953.8
PTEN	NM_001304717.5 linkuse as main transcript	c.*2185C>T	3_prime_UTR_variant	10/10
PTEN	NM_001304718.2 linkuse as main transcript	c.*2185C>T	3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTEN	ENST00000371953.8 linkuse as main transcript	c.*2185C>T		3_prime_UTR_variant	9/9	1	NM_000314.8	P1	P60484-1

Frequencies

GnomAD3 genomes

AF:

0.0681

AC:

10326

AN:

151706

Hom.:

418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.0749

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0464

Gnomad FIN

AF:

0.0737

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0657

Gnomad OTH

AF:

0.0733

GnomAD4 exome

AF:

0.0707

AC:

4820

AN:

68142

Hom.:

170

Cov.:

AF XY:

0.0718

AC XY:

2268

AN XY:

31572

show subpopulations

Gnomad4 AFR exome

AF:

0.0469

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.0602

Gnomad4 EAS exome

AF:

0.0859

Gnomad4 SAS exome

AF:

0.0478

Gnomad4 FIN exome

AF:

0.0945

Gnomad4 NFE exome

AF:

0.0659

Gnomad4 OTH exome

AF:

0.0709

GnomAD4 genome

AF:

0.0680

AC:

10330

AN:

151824

Hom.:

419

Cov.:

AF XY:

0.0687

AC XY:

5097

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0428

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.0594

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.0462

Gnomad4 FIN

AF:

0.0737

Gnomad4 NFE

AF:

0.0657

Gnomad4 OTH

AF:

0.0726

Alfa

AF:

0.0678

Hom.:

537

Bravo

AF:

0.0734

Asia WGS

AF:

0.0690

AC:

239

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PTEN hamartoma tumor syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over